Méndez-Sánchez N

Language: English
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Page: 88
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The aim of this study was to examine the pharmacokinetics of acemetacin and of its active metabolite, indomethacin, during the necrotic and regenerative processes occurring after the induction of acute hepatitis by CCl4 in the rat, a widely accepted experimental model of liver damage. They found that one day after CCl₄ administration, liver necrosis was apparent and there was an increase in the circulating levels of indicators of liver damage and regeneration with regard to control conditions. By day 3, histological analysis revealed liver recovery, although not complete, while biochemical indicators of hepatic damage had reverted either totally or partially. Markers of liver regeneration were still increased. Bioavailability acemetacin and indomethacin was comparable to control values. The authors concluded that indomethacin bioavailability after oral administration of its precursor, acemetacin, is significantly reduced by acute hepatitis produced by CCl4. Pharmacokinetic alterations, as liver damage, are reversible, but do not require complete liver regeneration to return to basal conditions.